Dysfunctional uterine bleeding (DUB) is excessive and prolonged or frequent bleeding that is not caused by pregnancy or disease. It may include abnormal or increased menstrual flow, or unexplained menorrhagia, which may include mild to severe clotting and last longer than 7 days. DUB may also be associated with unexplained anovulatory bleeding. Generally, DUB occurs in pubescent or peri-menopausal women, but may occur in women of any age. If left untreated, DUB may lead to iron deficiency, and eventually anemia.
The objectives for treating DUB include control of an acute bleeding episode and prevention of the reoccurrence of acute bleeding episodes. Several pharmaceuticals and pharmaceutical regimens are well-known for use in the treatment of DUB. For example, many women have been treated by the combination therapy of the administration of estrogen and progestin. Such combinations are often found in pharmaceuticals generally prescribed for oral contraception and hormone replacement therapy in menopausal women. DUB has also been treated with GnRH analogs, non-steroidal anti-inflammatory drugs or androgens. Surgical treatments, such as dilation and curettage (D&C) or hysterectomy have also been used in some cases to treat DUB, although surgical methods are very invasive and are typically avoided if treatment is possible through administration of pharmaceuticals.
Commercially available oral contraceptives that contain a combination of norethindrone acetate and ethinyl estradiol (combination estrogen and progestin product) have been used to treat DUB. However, the low daily dosages of estrogen and progestin in combination oral contraceptives, which limit the side effects caused by higher dosages while still providing effective contraception, are not sufficient for the treatment of an acute episode of DUB. Several treatment regimens for DUB utilizing combination oral contraceptive tablets have been described, but typically one to four combination oral contraceptive tablets must be taken per day for five to seven days to effectively stop the acute bleeding, followed by at least one twenty-eight-day pack of oral contraceptive tablets with one tablet administered daily. Further, research shows that the use of progestins alone, such as norethindrone acetate or medroxyprogesterone acetate, to treat DUB is associated with less nausea and vomiting and may be associated with a lower risk to patients of venous thromboembolism than either high dose estrogen given alone or in combination with a progestin.
For example, it is known to treat DUB by administering a daily dosage of either norethindrone acetate or medroxyprogesterone acetate, where the daily dosage is the same on some days and different on others. When multiple doses are taken on the same day, patients are generally encouraged to space the dosages throughout the day. As a result, patients need to keep track of which day of the regimen it is, how many pills to take that day and when to take them. Further complicating this treatment is that the prescribed oral dosages of norethindrone acetate and medroxyprogesterone acetate are in an amount greater than that usually provided in oral contraceptives (such as 5 mg tablets of norethindrone acetate or 10 mg tablets of medroxyprogesterone acetate). Consequently, they are presently only dispensed to patients in bulk, meaning multiple pills in a single bottle. Generally, the pill bottle will be supplied by the pharmacist with the instructions for the prescribed dosage on the bottle and with enough tablets included to last for the entire duration of the regimen. Because the tablets are dispensed in bulk, it is difficult for patients to properly comply with the complex dosage regimen prescribed for DUB. Lack of proper compliance can cause recurrence of the DUB symptoms and may lead to more invasive treatment such as surgery. Also, lack of compliance among patients limits a physician's ability to determine the effectiveness of the regimen prescribed for an individual patient or for research purposes. Further, a single pill bottle full of pills makes it difficult for a patient to remember if a particular dosage has already been taken on a particular day, thus creating a high probability of improper dosing. Hence, the need exists for a simple, yet effective means of simply and accurately dispensing a regimen for the treatment of DUB which has the likelihood of increasing patient compliance.